Assessing the causal relationship between 731 immunophenotypes and the risk of lung cancer: a bidirectional mendelian randomization study

Abstract

Background Previous studies have observed a link between immunophenotypes and lung cancer, both of which are closely associated with genetic factors. However, the causal relationship between them remains unclear. Methods Bidirectional Mendelian randomization (MR) was performed on publicly available genome-wide association study (GWAS) summary statistics to analyze the causal relationships between 731 immunophenotypes and lung cancer. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and potential horizontal pleiotropy of our findings. Results Following Bonferroni adjustment, CD14− CD16+ monocyte (OR = 0.930, 95%CI 0.900–0.960, P = 8.648 × 10− 6, PBonferroni = 0.006) and CD27 on CD24+ CD27+ B cells (OR = 1.036, 95%CI 1.020–1.053, P = 1.595 × 10 − 5, PBonferroni = 0.012) were identified as having a causal role in lung cancer via the inverse variance weighted (IVW) method. At a more relaxed threshold, CD27 on IgD+ CD24+ B cell (OR = 1.035, 95%CI 1.017–1.053, P = 8.666 × 10− 5, PBonferroni = 0.063) and CD27 on switched memory B cell (OR = 1.037, 95%CI 1.018–1.056, P = 1.154 × 10− 4, PBonferroni = 0.084) were further identified. No statistically significant effects of lung cancer on immunophenotypes were found. Conclusions The elevated level of CD14− CD16+ monocytes was a protective factor against lung cancer. Conversely, CD27 on CD24+ CD27+ B cell was a risk factor. CD27 on class-switched memory B cells and IgD+ CD24+ B cells were potential risk factors for lung cancer. This research enhanced our comprehension of the interplay between immune responses and lung cancer risk. Additionally, these findings offer valuable perspectives for the development of immunologically oriented therapeutic strategies.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target

“…Thus, the findings should be generalized to other ancestries with caution. While the significance association of our MR results is supported by the currently recognized principal method, the IVW approach [ 29 , 48 , 49 ], and validated in another independent dataset, not all five MR methods consistently yielded significant associations. These varying OR values may reflect the different handling of statistical assumptions, confounding factors, and genetic heterogeneity by different methods [ 50 – 52 ].…”